GLP-1/GLP-1R Signaling in Regulation of Adipocyte Differentiation and Lipogenesis

Abstract

Key Words Liraglutide • 3T3-L1 preadipocytes • Adipogenesis • FASN AbstractBackground/Aims: The aim of this study was to determine the direct role of liraglutide (LG) in adipogenesis and lipid metabolism. Methods: Lipid accumulation was evaluated by oil red O staining, quantitative real-time PCR (qPCR) was performed to determine glucagon-like peptide 1 receptor (GLP-1R), fatty acid synthase (FASN) and adipose triglyceride lipase (ATGL) expression in 3T3-L1 preadipocytes, differentiated adipocytes and in adipose tissues from mice. The effects of LG on 3T3-L1 adipogenesis and lipid metabolism were analyzed with qPCR, Western Blotting, oil red O staining, immunohistochemistry (IHC) and immunofluorescence (IF). All measurements were performed at least three times. Results: LG increased the expression of differentiation marker genes and lipid accumulation during preadipocyte differentiation. In differentiated adipocytes, LG decreased FASN expression, and simultaneously led to CREB phosphorylation and ERK1/2 activation which were abolished by a GLP-1R antagonist, exendin (9-39).LG induced-FASN down-regulation was partially reversed by PKA and ERK1/2 inhibitors. Consistent with above in vitro findings, LG treatment significantly reduced FASN expression in visceral adipose tissues of ob/ob mice, and reduced body weight gain. Conclusion: LG promotes preadipocytes differentiation, and inhibits FASN expression in adipocytes.LG induced down-regulation of FASN is at least partially mediated by PKA and MAPK signaling pathways.

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“…Because of the key role played by GLP-1 in mediating lipid metabolism, much researches has aimed to understand the cellular and molecular mechanisms involved [18,19,40]. Fat accumulation in the liver is regarded as a key pathogenic factor of metabolic diseases.…”

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